The repair of bone defects can be facilitated by placing a bone repair material as a temporary substitute in the defect site, where a loss of natural bone has occurred. The bone repair material is meant to selectively promote and guide the regeneration of natural bone structures.
Both naturally-derived and synthetically-produced bone repair materials have been used to repair such defects. Naturally-derived materials include grafts made from bones. The bone may be harvested directly from the patient, as in autograft-based procedures, or it may be harvested from a suitable donor, surrogate, or cadaver, as in allograft- or xenograft-based procedures. Naturally-derived bone repair materials are usually prepared by acid extraction of most of the mineralized component to result in so called demineralized bone matrix (DBM). Examples for naturally-derived materials are Bio-Oss® of the mineral portion of bovine bone or Algipore® a porous calcium phosphate material of algae. Autologous bone is an ideal source of graft material, not only due to its biocompatibility, but also because natural bone grafts facilitate reossification of the defect site by promoting or conducting ingrowth of the patient's own bone tissue to the defect site. Autologous bone material inherently is osteoconductive and osteoinductive, two properties facilitating regeneration of natural bone structure. However, autograft bone implant procedures are costly and cause additional discomfort for the patient, as they typically require an additional surgery for harvesting the graft material, which may cause significant morbidity at the donor site. Autografts may also show pronounced resorption making the outcome of the augmentation unpredictable. Allogenic bone repair materials also unify osteoconductive and osteoinductive properties, but their origin raises possible pathogenic transfers and ethical issues. Similar concerns are brought up against xenogenic graft materials.
Alternatively, naturally-derived bone repair materials may be replaced by a completely synthetic bone repair material, which contains no organic residues. In contrast to naturally-occurring bone repair materials, synthetic bone repair materials are often less osteoconductive and hardly osteoinductive. Nevertheless, much research has been and still is directed toward improved synthetic bone repair materials.
In oral surgery and orthopedics, synthetic bone repair materials on a hydroxyapatite (HA) and/or tricalcium phosphate (TCP) basis are widely used. Depending on indications, they may be applied as granules or pre-fabricated blocks. U.S. Pat. No. 6,511,510 relates to a porous ceramic material from calcium phosphates obtained by a sintering process. The use of granular material allows treatment of a wide range of indications. For granular material, the ceramic block material is processed by steps such as rubbing, pounding and sieving afterwards (WO 04/054633). Although the granular materials are applied to a wide range of indications in terms of size and area, their suitability to treat large bone defects is limited, because they tend to migrate and as a result to be encapsulated. The augmented volume defined by the applied granules may collapse and fail to guide regrowth of the bone to its original dimensions. U.S. Pat. No. 7,012,034 describes a block-shaped bone augmentation material based on porous β-tricalcium phosphate.
Different approaches addressed the problem of providing a material with bone-like mechanical properties. In U.S. Pat. No. 6,994,726 a prosthetic bone implant is made of a hardened calcium phosphate cement having an apatitic phase as a major phase, which comprises a dense cortical portion bearing the majority of load, and a porous cancellous portion allowing a rapid blood/body fluid penetration and tissue ingrowth. Alternatively, EP 1457214 discloses a block shape organic-inorganic complex porous article with a superposed skin layer made of a degradable polymer with improved strength. The complex is mainly designed to be inserted between vertebral bodies.
To generally improve load bearing properties of bone repair materials, composite materials have been developed. EP 1374922 discloses a bioresorbable structure for use in the repair of bone defects comprising a porous bioceramic matrix of hydroxyapatite or tricalcium phosphate and a polymer disposed by compression moulding therein. WO 97/34546 describes a ceramic block with a plurality of channels filled containing an enforcing bio-resorbant polymer material. In order to improve their regenerative potential, bone repair materials have been supplemented with bone growth inducing agents. U.S. Ser. No. 10/271,140 (US2003/0143258A1) suggests a composite comprising demineralized bone matrix mixed with a stabilizing biodegradable polymer and a bone growth factor.
In a typical periodontal surgical bone repair procedure an incision is made in the gum tissue to expose a bone defect adjacent to a tooth root. Once the defect and root are debrided, a bone repair material, suspended in a suitable carrier is placed. The gum tissue is then closed, maintaining the repair material in place. Optionally, a barrier material may be utilized to retain the repair formulation in contact with the defect. Therefore, a bone repair material in periodontal surgery requires formulations that can be easily shaped to size and shape of the defect. WO 2004/011053 suggests a formulation with a putty consistency. Similarly, EP1490123 describes a kneadable and pliable bone replacement material on a granular calcium phosphate and hydrogel basis. When applied to the defect site, the formulation remains adhered thereto without migration or excessive expansion. These concepts however, do provide for a solid bone substitute material.